罗红霉素主要代谢产物的体外抗菌活性研究

临床上广泛使用的 (E) -罗红霉素在人体内有多种代谢途径。在鉴别和制备其代谢产物的基础上 ,采用二倍稀释法 ,选用 3种生物检测实验标准菌株 ,测定了母体药物和 6种主要代谢产物的体外抗菌活性(MIC,MBC)。结果表明 ,(E) -罗红霉素经代谢转化后 ,生成的 (Z) -罗红霉素异构体的活性略下降 ,(E) -红霉素肟的活性无明显改变 ,(E) - O-单去甲罗红霉素的 MIC未改变 ,而对芽孢杆菌的 MBC有所降低 ,(E) - N-单去甲罗红霉素的活性显著降低 ,(E) -脱红霉糖罗红霉素则基本失活。被测药物及代谢物在不同菌株之间的MIC和 MBC变化趋势基本相同 ,MBC较相应的 MIC大 10 0～ 10 0 0倍左右。

In vitro antibacterial activity of roxithromycin and its major metabolites

Several metabolic pathways of (E) roxithromycin, a widely used antibiotic, were observed in humans. On the basis of identification and preparation of the metabolites, the in vitro antibacterial activity (MIC, MBC) of the parent drug and its six major metabolites was determined by the 2 fold broth dilution method using three standard strains for biological assay. It was shown that after biotransformation of (E) roxithromycin, the antibacterial activity of the resultant isomer (Z) roxithromycin reduced slightly, while the activity of (E) erythromycin oxime and (Z) erythromycin oxime was not significantly changed; the MIC of (E) O demethyl roxithromycin remained the same, but its MBC to bacilli was reduced; the activity of (E) N demethyl roxithromycin was significantly lower than the parent drug, and decladinose roxithromycin was almost inactive. The MBCs and MICs of the tested compounds to the strains were mainly parallel, where the former was 100~1000 times higher than the latter, respectively.